MassMatrix is a newly developed database search software package for tandem mass spectrometric data. It uses a mass accuracy sensitive probabilistic scoring model to rank peptide and protein matches. MassMatrix provides improvements in sensitivity over Mascot and SEQUEST with comparably low false positives. MassMatrix has additional capabilities that set it apart for other algorithms. It is capable of searching through hierarchical MSn (n>=3) spectra (useful in phosphopeptide analysis) where higher confidence in peptide ID can be achieved over MS2 alone. The algorithm is also capable of direct searching of disulfide or chemical cross-linked peptides.